Lines of Sight: Biomaterials Deliver Cells to Treat Ocular Disease

Using biomaterials – anything engineered to work with your body to diagnose or treat disease and injury – is as old as the ancient Egyptians, who used animal sinew to stitch up their wounds. Biomaterials science as a formal discipline emerged more than a half century ago, and has grown to involve overlapping interests in chemistry, medicine, biology, physics, engineering and regenerative medicine.

More recently, researchers and clinicians who specialize in treating degenerative eye diseases have been looking for ways to develop cell therapies to maintain vision or restore lost sight. Enter McMaster University’s Dr. Heather Sheardown, a biomaterials and tissue engineering expert searching for ways to deliver those potential therapies to maximize their effectiveness.

1. Biomaterials can play a key role in regenerative medicine (RM) research to deliver and support cells to repair tissue. How has their use in RM evolved?

Dr. Sheardown: Biomaterials have played a significant role in RM right from the start, given their potential for delivering the right number of healthy cells to a location of interest to give them the best chance of success for integration to regenerate and repair damaged or diseased tissue.
These materials can be engineered from natural sources such as collagen, which is found in the skin and tendons of animals, and hyaluronic acid, which is found in skin, organs, and other parts of the body. Both can be manipulated to create effectively an extracellular matrix – the medium that helps cells grow and attach, and that regulates their behaviour – for cell delivery. However, natural sources tend to be more difficult to work with because of their variability; we can’t necessarily count on the collagen we use at one point in a study being the same as what we get at a later point. So, there has been a lot of progress in developing synthetic biomaterials, which is what my lab focuses on, from things like polylactic acid and more recently other novel, degradable materials. These are all well established for use in treating patients in other situations such as repairing burned skin, delivering drugs, implanting heart valves and other uses – we are adapting them for delivering cell therapies.

2. What are the potential advantages of using biomaterials to deliver cell therapies to treat ocular disease?

Dr. Sheardown: The challenge with treating ocular diseases is that it is difficult to access the delicate tissue and structures at the back of the eye. When treating diseases like age-related macular degeneration (AMD) and diabetic retinopathy, for example, physicians must use needles to deliver certain medications. We want to be able to deliver a bolus of cells and precisely control where they go and how they interact and integrate with the local tissues. Ultimately, our goal is to be able to effectively treat diseases of the retina such as AMD, diabetic retinopathy and neuropathy, and save a patient’s sight. If we can treat these conditions at an early enough stage, before the point of no return, we can potentially rescue diseased tissue. To do that, we need to stabilize the cells in the proper extracellular environment and deliver them effectively.

There are also potential applications for the front of the eye. If we can deliver stem cells to restore the cellular environment in the cornea earlier in the disease process and prevent the need for corneal transplant or provide new options for patients whose transplant has failed, it could have a huge impact on these patients as well as on the healthcare system.

3. Tell us about the multidisciplinary nature of your work.

Dr. Sheardown: I pride myself on being able to speak multiple “languages” among various scientific and clinical disciplines. We’re not a stem cell lab – we focus on materials that will support cellular function, extracellular matrix production, growth factors and other things. For example, we are developing liquid materials that can be mixed with cells and injected by a surgeon with precision into retinal tissue to restore function. We are also looking at things like new ways of delivering and integrating limbal stem cells via novel contact lens materials into the cornea to keep it from deteriorating to the point where it no longer functions.

It’s helpful for us to be able to talk with chemical engineers who tell us about new approaches to solve certain challenges we come across from a chemistry perspective, or to biologists who bring us problems to solve around creating certain cellular environments to support their work. We also work with the ultimate end-users, ophthalmologists and optometrists, because we can’t know the real-world challenges they face when treating patients. Before I started working closely with them, I was trying to solve problems in the literature, but they give me a clear sense of whether or not a certain approach is something they would actually use or not. They also clarify problems. I thought, for example, that one of the biggest issues to overcome is that patients don’t like getting a needle in the eye, but it turns out the distance they have to travel for treatment and the frequency of clinic visits are more important. That shapes our goals, for instance to be able to deliver therapy that lasts for a longer period of time. It’s all about looking at things through other people’s eyes.

4. How does Ontario’s RM ecosystem make your work possible as a basic scientist?

Dr. Sheardown: We always need more funding to do the things we need to do, but sometimes that forces us to pick our best ideas. Certainly, we are well ahead of other places in the world, and that has allowed organizations like OIRM, the Stem Cell Network and the Centre for Commercialization of Regenerative Medicine to flourish, which may not have been possible elsewhere. That’s been fantastic for us.

As researchers, I think we need to do better at communicating the value of what we all do at various stages, and that’s especially true for basic science. We get lost in trying to develop grand new treatments for disease, without providing the public and research funders a clear sense of all the little pieces that had to come together to make that jigsaw puzzle complete.